CHARACTERISTICS OF THE ALPHA-2-BETA-ADRENOCEPTOR-COUPLED ADENYLATE-CYCLASE SYSTEM AND THEIR RELATIONSHIP WITH ADRENERGIC RESPONSIVENESS IN HAMSTER FAT-CELLS FROM DIFFERENT ANATOMICAL SITES

Various studies have shown that the lipolytic response of white adipocytes to catecholamines was dependent on the anatomical origin of these cells. To provide a biological explanation for this phenomenon, we compared hamster white adipocytes, from femoral subcutaneous and epididymal fat, for their lipolytic activities, cAMP responses and adrenoceptor-coupled adenylate cyclase system. Basal and maximal lipolytic responses to the beta-adrenergic (isoproterenol) and the mixed alpha-2/beta-adrenergic (epinephrine) agonists were lower in femoral subcutaneous cells than in epididymal cells, but the alpha-2-adrenergic antilipolytic response to 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline bitartate (UK14304) was slightly greater in femoral subcutaneous fat cells than in epididymal fat cells. Identical results were observed for cAMP responses, except for the alpha-2-adrenergic inhibitory response which was identical in both fat deposits. Adrenoceptors studies revealed higher density of inhibitory alpha-2-adrenoceptors 2-(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline ([H-3]RX821002-binding sites) in femoral subcutaneous fat cells than in epididymal fat cells, but identical density of stimulatory beta-adrenoceptors (I-125-cyanopindolol-binding sites) and similar subdivision into beta-adrenoceptor subtypes in both adipose deposits. Finally, the level of the alpha-subunits of the stimulatory and inhibitors guanine-nucleotide-binding regulatory proteins, as well as the adenylate cyclase catalytic activity were 40-50% lower in femoral subcutaneous fat cell membranes than in epididymal fat cell membranes. These results suggest that the differences in cAMP and lipolytic responses to catecholamines between epididymal and femoral subcutaneous adipocytes result at least in part from site-related differences in the adenylate cyclase system rather than in the adrenoceptor status.